The Neonatal and Paediatric Pharmacokinetics of Antimicrobials study (NAPPA): investigating amoxicillin, benzylpenicillin, flucloxacillin and piperacillin pharmacokinetics from birth to adolescence.

BACKGROUND: Pharmacokinetic (PK) data underlying paediatric penicillin dosing remain limited, especially in critical care. OBJECTIVES: The primary objective of the Neonatal and Paediatric Pharmacokinetics of Antimicrobials study (NAPPA) was to characterize PK profiles of commonly used penicillins using data obtained during routine care, to further understanding of PK variability and inform future evidence-based dosing. METHODS: NAPPA was a multicentre study of amoxicillin, co-amoxiclav, benzylpenicillin, flucloxacillin and piperacillin/tazobactam. Patients were recruited with informed consent. Antibiotic dosing followed standard of care. PK samples were obtained opportunistically or at optimal times, frozen and analysed using UPLC with tandem MS. Pharmacometric analysis was undertaken using NONMEM software (v7.3). Model-based simulations (n = 10 000) tested PTA with British National Formulary for Children (BNFC) and WHO dosing. The study had ethical approval. RESULTS: For the combined IV PK model, 963 PK samples from 370 participants were analysed simultaneously incorporating amoxicillin, benzylpenicillin, flucloxacillin and piperacillin data. BNFC high-dose regimen simulations gave these PTA results (median fT>MIC at breakpoints of specified pathogens): amoxicillin 100% (Streptococcus pneumoniae); benzylpenicillin 100% (Group B Streptococcus); flucloxacillin 48% (MSSA); and piperacillin 100% (Pseudomonas aeruginosa). Oral population PK models for flucloxacillin and amoxicillin enabled estimation of first-order absorption rate constants (1.16 h-1 and 1.3 h-1) and bioavailability terms (62.7% and 58.7%, respectively). CONCLUSIONS: NAPPA represents, to our knowledge, the largest prospective combined paediatric penicillin PK study undertaken to date, and the first paediatric flucloxacillin oral PK model. The PTA results provide evidence supportive of BNFC high-dose IV regimens for amoxicillin, benzylpenicillin and piperacillin.

Evaluation of age-banded dosing of oral paracetamol in hospitalised children: a retrospective analysis using clinical data in a tertiary paediatric hospital.

OBJECTIVE: To evaluate age-banded dosing in paediatric inpatients by determining the proportion of patients whose dose would fall outside the therapeutic range (by weight). DESIGN: A retrospective observational study. Weight and height measurements and details of hospital admissions were matched from the electronic patient record of a single, tertiary paediatric hospital. Dosage which would be given according to age-banded dosing was then compared with their weight. PARTICIPANTS: All children admitted to a single tertiary children's hospital aged 3 months to 16 years over a 5-year period. Data were cleaned to remove values likely to be erroneous and filtered to reduce bias due to patients who were admitted on multiple occasions. OUTCOMES: The main outcome was the proportion of patients who would receive a subtherapeutic or supratherapeutic paracetamol dose if given a dose based on their age. Secondary outcomes were to examine this in children of different ages and to examine the impact of alternative size-based dosing strategies. RESULTS: 100 047 admissions (in 68 310 patients) had a weight documented. If age-banded dosing had been used, a subtherapeutic dose (less than 10 mg/kg) would be given during 19 829 (20%) of the admissions and a supratherapeutic dose (over 18.75 mg/kg, 75 mg/kg/day in four doses) in 4289 (4.3%). The highest risk of a subtherapeutic dose occurred in infants just prior to reaching 6 months of age (83%) and in children just prior to reaching 8 years (66%). The highest risk of a supratherapeutic dose was at 12 years of age (35%). CONCLUSION: Age-banded dosing is not suitable for an inpatient paediatric population as approximately a quarter of patients receive a dose outside the recommended range of 10.0-18.75 mg/kg.

How to spot a narcissist: Mental health literacy with respect to Narcissistic Personality Disorder.

Lay people were asked to read one Depression, one Schizophrenia, and three Narcissistic Personality Disorder (NPD) vignettes. After each, they were asked what they thought the problem was for the individuals concerned and to make various ratings. Half of each of the five vignettes were of male, and the other of female, characters. The results demonstrated that laypeople are less likely to suggest help for, and have more difficulty identifying NPD compared to Depression and Schizophrenia. There were differences in the likeliness to suggest help between all three NPD vignettes and differences in the identification of two NPD vignettes possible due to the length and details in different vignettes. The gender of the person in the vignette had no effect on identification. The participants NPI scores were not correlated with the Narcissism literacy suggesting no relationship between having, and spotting, the disorder. Implications and limitations of the research are considered.